A large study of multiple sclerosis patients, healthy siblings and patients with other neurological diseases has been performed, and the findings of our preliminary survey have been confirmed. Vaccinia antibodies are found more frequently and in higher titer in the CSF of patients with multiple sclerosis than either their healthy siblings or the other control group. Moreover there appears to be a significant correlation between the clinical character of the disease and the frequency and titer of CSF antibodies. It is proposed to expand on this study to include measurements of delayed hypersensitivity, tissue typing, and investigations in autopsy specimens of vaccinia and other viral antigens in the nervous tissue of multiple sclerosis patients and suitable control groups.